In an initial group of experiments, pineal N-acetyltransferase activity (NAT) was measured after pretreatment of rats with phenoxybenzamine (POB). Since POB stimulated NAT activity in light-treated rats and since propranolol prevents the effect of POB, it is likely that POB's ability to prevent the light-mediated decrease in NAT activity is by way of stimulatory action of the drug at the pineal beta-receptor. In vivo experiments demonstrating that ganglionectomy and adrenalectomy do not prevent the action of POB suggest that this effect is produced by direct action of the drug on the pineal beta-receptor and not an indirect action mediated by another central or peripheral mechanism. Experiments demonstrating stimulatory activity of POB on NAT activity in cultured pineals confirm this suggestion. In a second series of experiments the role of cyclic AMP in the rapid light-mediated decrease in NAT activity was investigated. The decrease in NAT activity was consistently accompanied by a decrease in cAMP content after one minute of light exposure to dark-adapted rats. This was followed by a more marked rise in cAMP content after 4-6 minutes. These changes in cAMP were prevented by pretreating rats with POB and were in part mimicked by propranolol.